Evidence for the role of nitric oxide in caffeine-induced locomotor activity in mice

Rationale. Nitric oxide (NO) is implicated in the acute locomotor activating effects of some addictive drugs such as amphetamine and cocaine, but has not been investigated in the case of caffeine. Objectives. We investigated the effects of a nitric oxide synthase (NOS) inhibitor Nomega-Nitro-L-arginine methyl ester L-NAME) and a combination of L-arginine, a NO precursor, and L-NAME on caffeine induced locomotor activity in Swiss Webster mice. Methods. Locomotor activity was recorded for 30 min immediately following caffeine (0.25-128 mg/kg) or saline administration. In a further study, L-NAME (15 and 30 mg/kg) was administered to another group of mice 30 min before caffeine (1 and 16 mg/kg) injections. Finally, L-arginine (1000 mg/kg), a nitric oxide precursor, was administered 20 min before the L-NAME (15 and 30 mg/kg) treatments and locomotor activities were again recorded immediately after caffeine (1 and 16 mg/kg) injections. Results. Caffeine (0.5-16 mg/kg) significantly increased locomotor activity, while L-NAME (30 mg/kg) blocked caffeine (1 and 16 mg/kg)-induced locomotor activity. The low dose of L-NAME blocked only caffeine (1 mg/kg)-induced locomotor activity. L-Arginine reversed the inhibitory effects of L-NAME on caffeine-induced locomotor activity. L-NAME and L-arginine had no effect on the locomotor activity of the mice when given by themselves. Conclusions. The results suggest that caffeine-induced locomotor activity might be modulated by NO in mice.